Prospective memory (ProM), which refers to the successful execution of a future intention (i.e., remembering to remember), plays a vital role in everyday functioning (e.g., remembering to attend medical appointments), maintaining optimal health (e.g., remembering to take medications), and enabling independent living (e.g., remembering to pay the household bills). The uniqueness of this construct is supported by research showing that ProM is separable from retrospective memory (and global cognitive functioning) at the neuropsychological, functional, and neurobiological levels. The scientific merits of examining ProM in HIV infection are fourfold: 1) it enhances our understanding of the cognitive systems affected by the disease; 2) it impacts public health by improving the early identification of neuropsychological and functional impairments, which remain prevalent in the era of combination antiretroviral therapies; 3) it advances standard clinical neuropsychological practice; and 4) it informs targeted treatments. The current R01 has yielded the first published evidence that HIV is associated with elevated ProM complaints and impaired ProM performance, which are functionally and neurobiologically distinct from HIV-associated deficits in retrospective memory. Importantly, HIV-associated ProM impairment is a unique and robust predictor of declines in daily functioning, demonstrating incremental ecological validity relative to traditional measures of retrospective memory, executive functions, and global cognitive impairment. A novel direction for this revised competing renewal, as supported by pilot data from the initial funding period, will be to examine the additive effects of aging on HIV-associated ProM impairment. The incidence and prevalence of HIV infection in older adults are rising and consequently of considerable public health importance. The study of ProM is highly relevant to older HIV-infected adults, who may be at greater risk for exacerbated HIV-associated CNS complications (e.g., dementia), which increases the likelihood of dependence in daily functioning (e.g., medication nonadherence). Although ProM is impaired in healthy older adults and persons with HIV infection, no studies to date have evaluated the combined effects of these risk factors on ProM. Accordingly, this competing renewal aims to extend the findings from the initial grant period by: 1) focusing on older adults with HIV, who are a growing but understudied population in the changing HIV epidemic; 2) expanding the study design to examine the incidence of ProM impairment and its risk factors; 3) broadening our conceptual model to include habitual ProM; and 4) examining an important new functional outcome, health-related quality of life. To accomplish these aims, we propose a 5-year, longitudinal study to evaluate 125 older HIV+, 75 older HIV-, 125 younger HIV+, and 75 younger HIV- volunteers on comprehensive neuropsychological, functional, psychiatric, and neuromedical assessments. This new direction of research aims to bolster the clinical value of HIV-associated ProM impairment as an early marker of functional declines (e.g., medication nonadherence) and poorer health outcomes in older HIV-infected adults, as well as to directly inform the development of targeted pharmacological and cognitive-behavioral therapies. PUBLIC HEALTH RELEVANCE This study will evaluate the combined effects of aging and HIV infection on prospective memory, which is a unique cognitive ability that describes one's ability to remember to remember and plays a vital role in performing normal daily functions, especially adhering to medications. As such, this project will identify the day- to-day impact of prospective memory impairment in older adults with HIV infection, including its relationship to medication adherence and quality of life. Findings from this study will help in the early detection of HIV- associated prospective memory impairment, as well as in the development of treatments designed to limit the everyday effects of such deficits on older adults with HIV infection and their care providers.